Biology Reference
In-Depth Information
ch
9
Antigen presentation and
antigen-presenting cells in
graft-versus-host disease
Christian A Wysocki
Allergy and Clinical Immunology Section, Department of Medicine, Yale University School of Medicine,
New Haven, Connecticut, USA
Warren D Shlomchik
Hematology Section, Department of Medicine, and Yale Comprehensive Cancer Center,
Yale University School of Medicine, New Haven, Connecticut, USA
173
Introduction
The precursor frequencies of T cells that recognize host minor histocom-
patibility antigens (miHAs) has been estimated to be between 1 in 10
5
and
1 in 10
6
[1]
. Yet, these relatively infrequent T cells, when transplanted into
an alloantigen-bearing host, undergo clonal expansion sufficient to release
high levels of systemic cytokines and cause widespread and persistent T-cell
infiltrative pathology. This chapter addresses the identities of the cells that
stimulate these T cells to divide and differentiate into graft-versus-host dis-
ease (GVHD) effectors. By convention, the diverse sets of cells that stimulate
T cells have been called “antigen-presenting cells” (APCs). Broadly, among
hematopoietic cells this includes dendritic cells (DCs), macrophages, B
cells, and basophils. The signals conveyed from APC to T cell are not limited
to binary “divide signals,” but include analog signals delivered by costimu-
latory molecules and cytokines, which govern the qualities of daughter T
cells—for example, the cytokines they produce, the homing molecules they
express, and the likelihood they will enter a program of memory cell dif-
ferentiation
[2-4]
. The outcome of activation may depend on the location
of the APC:T-cell interaction, the subclass of APC doing the priming, the
external stimuli received by both the T cell and the APC, and the presence of
immunosuppressive cells and molecules. A rationale for the detailed study
of APCs that initiate alloreactive donor T-cell activation is that the knowl-
edge gleaned could lead to novel immunosuppressive and immunostimu-
latory strategies. As is described in this chapter, much progress has been
made in this area, but important questions remain. An area less well inves-
tigated than the identities of cells that prime alloreactive T cells is the role
APCs that infiltrate GVHD target organs play in GVHD pathology. Such cells
and their interactions with T cells could be organ-specific targets of immu-
nosuppression that might not decrease graft-versus-leukemia responses.
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